Adjuvant Reirradiation With Proton Therapy in Head and Neck Squamous Cell Carcinoma.

Purpose: For patients with head and neck squamous cell carcinoma (HNSCC), locoregional failure and second primary tumors are common indications for adjuvant reirradiation (re-RT). Given an absence of clear consensus on the role of adjuvant re-RT, we sought to assess histopathologic risk factors of patients with HNSCC and their resulting outcomes after adjuvant re-RT with proton therapy. Methods and Materials: We conducted a retrospective analysis of patients with HNSCC who underwent salvage surgery at our institution followed by adjuvant re-RT with proton therapy over 1.5 years. All included patients received prior radiation therapy. The Kaplan-Meier method was used to evaluate locoregional recurrence-free survival and overall survival. Results: The cohort included 22 patients, with disease subsites, including oropharynx, oral cavity, hypopharynx, larynx, and nasopharynx. Depending on adverse pathologic features, adjuvant re-RT to 66 Gy (32% of cohort) or 60 Gy (68%), with (59%) or without (41%) concurrent systemic therapy was administered. The majority (86%) completed re-RT with no reported treatment delay; 3 patients experienced grade ≥3 acute Common Terminology Criteria for Adverse Events toxicity and no patient required enteral feeding tube placement during re-RT. Median follow-up was 21.0 months (IQR, 11.7-25.2 months). Five patients had biopsy-proven disease recurrences a median of 5.9 months (IQR, 3.8-9.7 months) after re-RT. Locoregional recurrence-free survival was 95.2%, 70.2%, 64.8% at 6, 12, and 24 months, respectively. OS was 100%, 79.2%, and 79.2% at 6, 12, and 24 months, respectively. Four patients had osteoradionecrosis on imaging a median of 13.2 months (IQR, 8.7-17.4 months) after re-RT, with 2 requiring surgical intervention. Conclusions: Adjuvant re-RT for patients with HNSCC was well-tolerated and offered reasonable local control in this high-risk cohort but appears to be associated with a risk of osteoradionecrosis. Additional study and longer follow-up could help define optimal patient management in this patient population.

Risk-Tailoring Radiotherapy for Endometrial Cancer: A Narrative Review.

Endometrial cancer is the most common gynecologic cancer in the United States and it contributes to the second most gynecologic cancer-related deaths. With upfront surgery, the specific characteristics of both the patient and tumor allow for risk-tailored treatment algorithms including adjuvant radiotherapy and systemic therapy. In this narrative review, we discuss the current radiation treatment paradigm for endometrial cancer with an emphasis on various radiotherapy modalities, techniques, and dosing regimens. We then elaborate on how to tailor radiotherapy treatment courses in combination with other cancer-directed treatments, including chemotherapy and immunotherapy. In conclusion, this review summarizes ongoing research that aims to further individualize radiotherapy regimens for individuals in an attempt to improve patient outcomes.

Gender Representation Among Academic US Radiation Oncology Department Chairs: Who are They?

Purpose: Women are underrepresented in academic radiation oncology (RO), particularly in leadership positions. In this study, we sought to better understand the characteristics of individuals who currently serve as academic RO chairpersons at institutions with an associated Accreditation Council for Graduate Medical Education-accredited RO residency training program. Methods and Materials: We created a database of academic RO chairpersons in the United States by using publicly available sources, including residency training program websites, hospital/institutional websites, Doximity, LinkedIn, the American Society for Radiation Oncology (ASTRO) website, the American College of Radiation Oncology website, and the National Plan and Provider Enumeration System National Provider Identifier Registry. We used the χ2 Goodness of Fit test, Mann-Whitney U test, and Fisher exact test via R version 4.1.1 to evaluate for statistical significance among categorical variables, medians, and proportions, respectively. Results: We identified 85 of the 90 chairpersons (94.4%) currently serving at institutions with an Accreditation Council for Graduate Medical Education-accredited RO residency training program, 5 of whom hold interim positions and were thus excluded from further analyses. Of the remaining 80 chairpersons, 9 (11.3%) are women, and 71 (88.8%) are men (P < .01). Seventy-six chairpersons (95.0%) are full professors, and 19 (23.8%) hold dual MD PhD degrees. Thirty-two chairpersons (40.0%) hold an official leadership role in a cancer center affiliated with their current institution (43.7% of men vs 11.1% of women; P = .08). Seventy-three chairpersons (91.3%) secured their current positions a median of 16 years (range, 6-33 years) after completing RO residency. Thirty-five chairpersons (43.8%) were promoted to chair from positions within their current institutions (40.8% of men vs 66.7% of women; P = .17). The majority of chairpersons are ASTRO Fellows (62.5%); notably fewer are ASTRO (5.0%) or American College of Radiation Oncology (2.5%) Gold Medalists. Eight RO residency programs trained more than half of current chairpersons. Conclusion: Significantly more men than women currently serve as RO chairpersons. Future interventions that promote the recruitment, retention, and promotion of talented women in academic RO should be considered.

The effects of radiation therapy on the heart: implications for management.

Chemotherapy, radiotherapy, and surgery constitute the three primary modalities employed in the treatment of patients with cancer. Radiotherapy, in particular, is a mainstay of treatment for patients with cancers of the breast, esophagus, lung, and lymph nodes. Prior studies have shown, however, that radiotherapy can impact the heart. Radiation exposure, in fact, can lead to pathophysiological changes that may result in short- and long-term radiation-induced cardiac toxicities. Such toxicities can cause substantial morbidity and may manifest clinically in the weeks to years after the completion of treatment. As a result, in both modern clinical practice and clinical trials, the heart has been recognized as an organ-at-risk, and radiotherapy treatment plans seek to minimize the dose that it receives. In this review, we focus on the impacts of radiotherapy on underlying cardiac risk factors, the pathophysiology of radiotherapy-induced cardiac changes, and the clinical impacts of radiotherapy on the heart. Due to the location of the heart, we focus primarily on patients who have received radiotherapy for cancers of the breast, esophagus, lung, and lymph nodes, and those who have received cardiac-directed therapy. We then elaborate on the ongoing attempts to further lower the doses delivered to the heart during therapeutic courses of radiation.

Head and Neck Cancer Patient Population, Management, and Oncologic Outcomes from the COVID-19 Pandemic.

The COVID-19 pandemic precipitated drastic changes in cancer care. Its impact on the U.S. head and neck cancer population has yet to be fully understood. This study aims to understand the impact of pandemic-related changes on the head and neck cancer population. An observational study of head and neck cancer patients at a single institution during the spring of 2020 and 2019 was performed. Clinical characteristics and survival outcomes were analyzed. In 2020, 54 head and neck cancer patients were evaluated in the department of radiation oncology vs. 74 patients seen in 2019; 42% of the patients were female in 2019 versus 24% in 2020 (p = 0.036). The median follow-up time was 19.4 and 31 months for 2020 and 2019, respectively. After adjusting for stage, the relapse-free survival probability at 6 and 12 months was 79% and 69% in 2020 vs. 96% and 89% in 2019, respectively (p = 0.036). There was no significant difference in the overall survival, with 94% and 89% in 2020 and 2019, respectively (p = 0.61). Twenty-one percent of patients received induction chemotherapy in 2020 versus 5% in 2019 (p = 0.011); significantly more treatment incompletions occurred in 2020, 9% vs. 0% in 2019 (p = 0.012). Moreover, the stage-adjusted RFS differed between cohorts, suggesting head and neck cancer patients seen during the initial wave of COVID-19 may experience worse oncologic outcomes.

Academic and Geographic Employment Outcomes for Graduating Residents in Radiation Oncology: 2015-2022.

PURPOSE: Little is known about how the academic and geographic employment outcomes of new radiation oncology (RO) graduates have changed over time. In this study, we sought to trace the evolution of these outcomes for all RO residents who graduated between 2015 and 2022. METHODS AND MATERIALS: Using publicly available data sources, we identified the first permanent, clinical employment positions accepted by graduating members of the RO residency classes of 2015 to 2022. We additionally determined the medical school and residency program attended by each graduate. We then classified each clinical employment position by its rural-urban continuum code and core-based statistical area, and whether it was academic or nonacademic. RESULTS: Of 1478 RO graduates identified, 1396 first accepted clinical positions in the United States after residency. A majority accepted positions in the largest metropolitan areas (N = 878, 62.9%) and in nonacademic settings (N = 719, 51.5%). The proportion of graduates who accepted academic positions climbed steadily from 2015 to 2020 before dropping by 31% in 2021 and partially rebounding in 2022. Women and graduates of large-sized academic programs were more likely to have accepted academic positions. In contrast, graduates of small-sized residency programs were more likely than those of large-sized residency programs to have accepted positions in nonmetropolitan areas. At least 288 of the examined individuals (20.6%) had switched jobs at least once at the time of this analysis. CONCLUSIONS: Most new RO graduates in this study accepted clinical positions in large metropolitan areas. A slight majority accepted nonacademic positions. While the RO job market was able to absorb the vast majority of these new graduates between 2015 and 2022, there is no guarantee that this equilibrium will hold in the future. Additional studies aiming to refine projections of future RO demand are needed.

Dose and fractionation regimen for brachytherapy boost in cervical cancer in the US.

PURPOSE: Curative-intent radiotherapy for locally advanced and select early stage cervical cancer in the US includes external beam radiotherapy (EBRT) with brachytherapy. Although there are guidelines for brachytherapy dose and fractionation regimens, there are limited data on practice patterns. This study aims to evaluate the contemporary utilization of cervical cancer brachytherapy in the US and its association with patient demographics and facility characteristics. METHODS: We retrospectively analyzed clinical covariates of cervical cancer patients diagnosed and treated in 2018-2020 with curative-intent radiotherapy from the 2020 National Cancer Database. Associations between patient and institutional factors with the number of brachytherapy fractions were identified with logistic regression. Factors with association (p < 0.10) were then included in a multivariable logistic regression model. All tests were two-sided with significance <0.05 unless specified otherwise. RESULTS: Among the eligible 2517 patients, 97.3% received HDR or LDR and is further analyzed. More patients received HDR than LDR brachytherapy (98.9% vs 1.1%) and intracavitary than interstitial brachytherapy (86.4% vs 13.6%). The most common number of HDR fractions prescribed were 5 (51.0%), 4 (32.9%), and 3 (8.6%). After adjusting for the other variables in the model, ethnicity, private insurance status, overall insurance status, and facility type were the only factors that were significantly associated with the number of brachytherapy factions (p < 0.0001, p = 0.028, p = 0.001, and p < 0.0001, respectively, n = 2184). CONCLUSIONS: In the US, various HDR brachytherapy regimens are utilized depending on patient and institutional factors. Future research may optimize cervical cancer brachytherapy by correlating specific dose and fractionation regimens with patient outcomes.

Immune Escape in Glioblastoma: Mechanisms of Action and Implications for Immune Checkpoint Inhibitors and CAR T-Cell Therapy.

Glioblastoma, the most common primary brain cancer in adults, is characterized by a poor prognosis and resistance to standard treatments. The advent of immunotherapy has revolutionized the treatment of several cancers in recent years but has failed to demonstrate benefit in patients with glioblastoma. Understanding the mechanisms by which glioblastoma exerts tumor-mediated immune suppression in both the tumor microenvironment and the systemic immune landscape is a critical step towards developing effective immunotherapeutic strategies. In this review, we discuss the current understanding of immune escape mechanisms in glioblastoma that compromise the efficacy of immunotherapies, with an emphasis on immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy. In parallel, we review data from preclinical studies that have identified additional therapeutic targets that may enhance overall treatment efficacy in glioblastoma when administered alongside existing immunotherapies.

Effects of trauma history on cancer-related screening, diagnosis, and treatment.

Trauma has substantial effects on human health and is recognised as a potential barrier to seeking or receiving cancer care. The evidence that exists regarding the effect of trauma on seeking cancer screening, diagnosis, and treatment and the gaps therein can define this emerging research area and guide the development of interventions intended to improve the cancer care continuum for trauma survivors. This Review summarises current literature on the effects of trauma history on screening, diagnosis, and treatment among adult patients at risk for or diagnosed with cancer. We discuss a complex relationship between trauma history and seeking cancer-related services, the nature of which is influenced by the necessity of care, perceived or measured health status, and potential triggers associated with the similarity of cancer care to the original trauma. Collaborative scientific investigations by multidisciplinary teams are needed to generate further clinical evidence and develop mitigation strategies to provide trauma-informed cancer care for this patient population.

Durvalumab Treatment Patterns for Patients with Unresectable Stage III Non-Small Cell Lung Cancer in the Veterans Health Administration (VHA): A Nationwide, Real-World Study.

BACKGROUND: Durvalumab is approved for the treatment of adults with unresectable stage III non-small cell lung cancer (NSCLC) post-chemoradiotherapy (CRT). This real-world study describes patient characteristics and durvalumab treatment patterns (number of doses and therapy duration; treatment initiation delays, interruptions, discontinuations, and associated reasons) among VHA-treated patients. METHODS: This was a retrospective cohort study of adults with unresectable stage III NSCLC receiving durvalumab at the VHA between 1 January 2017 and 30 June 2020. Patient characteristics and treatment patterns were presented descriptively. RESULTS: A total of 935 patients were included (median age: 69 years; 95% males; 21% Blacks; 46% current smokers; 16% ECOG performance scores ≥ 2; 50% squamous histology). Durvalumab initiation was delayed in 39% of patients (n = 367). Among the 200 patients with recorded reasons, delays were mainly due to physician preference (20%) and CRT toxicity (11%). Overall, patients received a median (interquartile range) of 16 (7-24) doses of durvalumab over 9.0 (2.9-11.8) months. Treatment interruptions were experienced by 19% of patients (n = 180), with toxicity (7.8%) and social reasons (2.6%) being the most cited reasons. Early discontinuation occurred in 59% of patients (n = 551), largely due to disease progression (24.2%) and toxicity (18.2%). CONCLUSIONS: These real-world analyses corroborate PACIFIC study results in terms of the main reasons for treatment discontinuation in a VHA population with worse prognostic factors, including older age, predominantly male sex, and poorer performance score. One of the main reasons for durvalumab initiation delays, treatment interruptions, or discontinuations was due to toxicities. Patients could benefit from improved strategies to prevent, identify, and manage CRT and durvalumab toxicities timely and effectively.

Combining Radiotherapy and Immunotherapy in Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is a leading cause of morbidity and mortality globally. Despite significant advances in well-established treatment techniques, prognosis for advanced-stage HNSCC remains poor. Recent, accumulating evidence supports a role for immunotherapy in HNSCC treatment. Radiation therapy (RT), a standard treatment option for HNSCC, has immunomodulatory and immunostimulatory effects that may enhance the efficacy of immunotherapy. In several cancer types, combining RT and immunotherapy has been shown to improve tumor response rates, increase survival, and reduce toxicity compared to traditional chemotherapy and radiation therapy. This review provides a timely overview of the current knowledge on the use of RT and immunotherapy for treating HNSCC. It highlights the potential advantages of combining these therapies, such as improved tumor response rates, increased survival, and reduced toxicity. The review also discusses the challenges that need to be addressed when redefining the standard of care in HNSCC, and proposes further research to optimize treatment combinations, minimize radiation-induced toxicity, and identify suitable patient populations for treatment.

The Impact of Medicaid Expansion on Patients with Cancer in the United States: A Review.

Since 2014, American states have had the option to expand their Medicaid programs as part of the Affordable Care Act (ACA), which was signed into law by former President Barack H. Obama in 2010. Emerging research has found that Medicaid expansion has had a significant impact on patients with cancer, who often face significant financial barriers to receiving the care they need. In this review, we aim to provide a comprehensive examination of the research conducted thus far on the impact of Medicaid expansion on patients with cancer. We begin with a discussion of the history of Medicaid expansion and the key features of the ACA that facilitated it. We then review the literature, analyzing studies that have investigated the impact of Medicaid expansion on cancer patients in terms of access to care, quality of care, and health outcomes. Our findings suggest that Medicaid expansion has had a positive impact on patients with cancer in a number of ways. Patients in expansion states are more likely to receive timely cancer screening and diagnoses, and are more likely to receive appropriate cancer-directed treatment. Additionally, Medicaid expansion has been associated with improvements in cancer-related health outcomes, including improved survival rates. However, limitations and gaps in the current research on the impact of Medicaid expansion on patients with cancer exist, including a lack of long-term data on health outcomes. Additionally, further research is needed to better understand the mechanisms through which Medicaid expansion impacts cancer care.

Radiotherapy and Immunotherapy in Lung Cancer.

The emergence of immune checkpoint inhibitors (ICIs) as a pillar of cancer treatment has emphasized the immune system's integral role in tumor control and progression through cancer immune surveillance. ICIs are being investigated and incorporated into the treatment paradigm for lung cancers across stages and histology. To date, definitive concurrent chemoradiotherapy followed by consolidative durvalumab is the only National Comprehensive Cancer Network's recommended treatment paradigm including radiotherapy with ICI in lung cancers, although there are other recommendations for ICI with chemotherapy and/or surgery. This narrative review provides an overall view of the evolving integration and synergistic role of immunotherapy and radiotherapy and outlines the use of immunotherapy with radiotherapy for the management of small cell lung cancer and non-small cell lung cancer. It also reviews selected, practice-changing clinical trials that led to the current standard of care for lung cancers.

Gender Differences in the Research Productivity of Radiation Oncology Resident Graduates in the United States: 2015 to 2019.

Purpose: It is well-documented that gender disparities exist in academic radiation oncology departments. The purpose of this study was to analyze gender differences in research productivity during residency among recent graduates of radiation oncology training programs in the United States (US). Methods and Materials: We used several publicly available sources to create a database of US radiation oncology residents who graduated between 2015 and 2019. We systematically collected gender information from the National Plan and Provider Enumeration System National Provider Identifier Registry and Medicare claims registry. Postresidency employment information was collected using several publicly available sources. PubMed was queried to identify first-author publications of residents. A secondary analysis of metadata including impact factor, number of citations, modified Hirsch index (h index), and type of publication was performed. A multivariable linear regression was performed to evaluate the effect of gender on research productivity during residency. Results: There were 910 total graduates identified during this period and who were entered into this database, of whom all had available gender information. Female trainees comprised 29.0% (n = 264) of RO residents and had fewer first-author publications and citations, had lower mean modified h index, and were published in journals with lower impact factors. On multivariable linear regression analysis, female gender was independently associated with decreased total number of publications (P = .005), mean number of citations (P < .001), and modified h index (P = .001) when controlling for residency size and advanced (PhD or master's) degrees. Conclusions: In the US, female RO trainees had lower research productivity, which was not explained by advanced degrees or residency size. A significant gender gap in trainee research productivity persists, which has known implications in terms of academic achievement, promotions, and career trajectory. Future interventions to improve resident research productivity and mentorship are warranted.

Geographic Employment Outcomes for Graduating Residents in Radiation Oncology: 2021.

PURPOSE: In light of the persistent disparity in the prevalence of radiation oncologists between rural and urban areas in the United States, we sought to characterize the geographic employment outcomes of the radiation oncology (RO) residency class of 2021. METHODS AND MATERIALS: We identified the employment positions accepted by 2021 RO residency graduates using publicly available information. Then, we classified each position as academic or nonacademic and determined the rural-urban continuum code and core-based statistical area (CBSA) of each position, residency program, and medical school associated with the 2021 graduates. Last, we compared the geographic employment outcomes of the 2021 class with those of the 2019 class. RESULTS: Most 2021 graduates accepted employment positions outside of the counties, CBSAs, and states in which they attended medical school or residency. A total of 116 graduates accepted nonacademic positions, and 65 graduates accepted academic positions. Nine graduates accepted fellowships and were excluded from this analysis. As with the class of 2019, most 2021 graduates (n = 104; 57.5%) accepted positions in the largest metropolitan areas, and few (n = 11; 6.1%) accepted positions in nonmetropolitan areas. Female residents were more likely to accept academic (48.9% vs 31.3%; P = .03) and academic main site (36.2% vs 21.6%; P = .05) positions than male residents. The distribution of jobs in both the 5 and 10 largest CBSAs was not significantly different from what would have been expected if jobs were equally distributed across the country on the basis of population (P = .81 and P = .87, respectively). However, the distribution was significantly different from what would have been expected if the distribution of such positions reflected the number of residents who graduated from residency programs in those CBSAs (P < .01 and P < .01, respectively). CONCLUSIONS: As with the class of 2019, the majority of graduates in the class of 2021 accepted employment positions in large metropolitan areas. Relatively few graduates accepted positions in nonmetropolitan areas. How key RO stakeholders respond to the challenge of maintaining a stable supply of rural radiation oncologists while also ensuring that jobs available to graduating RO residents reflect their preferences will have a significant effect on the field going forward.

Management of Older Adults with Locally Advanced Head and Neck Cancer.

Thirty percent of patients with head and neck squamous cell carcinoma (HNSCC) are at least 70 years of age. This number continues to rise as life expectancy continues to increase. Still, older adults with HNSCC remain underrepresented in clinical trials, resulting in ambiguity on optimal management. Older adults are a complex patient population, often requiring increased support due to issues relating to functional and performance status, medical comorbidities, and medication management. Furthermore, in older adults with HNSCC, many of these conditions are independently associated with increased toxicity and worse outcomes. Toxicity in the older adult remains difficult to predict and to understand, and as treatment decisions are based on treatment tolerability, it is essential to understand the toxicities and how to minimize them. Novel predictive scores are being developed specifically for older adults with HNSCC to understand toxicity and to assist in personalized treatment decisions. There are clinical trials presently underway that are investigating shortened radiation courses and novel, less toxic systemic treatments in this population. In the forthcoming sections, we provide a detailed overview of the clinical data, treatment paradigms, and considerations in this population. This review provides a comprehensive overview of existing clinical data and clinical considerations in the older adult head and neck cancer population. Additionally, we provide a detailed overview of pertinent current and ongoing clinical trials, as well as future areas for investigation.

Radiation Oncologists' Views on Breast Radiation Therapy Guidelines: Utilizing an Online Q&A Platform to Assess Current Views on Whole-Breast Irradiation Therapy.

INTRODUCTION: Poor adherence to the 2011 American Society for Radiation Oncology (ASTRO) evidence-based guideline on whole-breast irradiation (WBI) has been reported. We utilized theMednet to assess the views of the updated 2018 guideline among radiation oncologists (ROs). METHODS: We identified 11 questions asked by community ROs on theMednet, a web-based platform, between October 27, 2014 and May 2, 2017 that were updated in the 2018 guideline. New answers provided by senior authors of the 2018 guideline, cited guidelines, and polls to survey ROs were disseminated in 3 theMednet's newsletters between March 16, 2018 and May 1, 2018. Any question with less than 60% consensus was resubmitted on October 9, 2019 and assessed on February 13, 2020. RESULTS: A total of 792 ROs responded to the initial surveys. In each survey, the answer choice(s) that received the majority of the votes aligned with the 2018 guideline. The strongest consensus was for the use of hypofractionated (HF)-WBI regardless of histology (97%), followed by HF-WBI boost dose (92%), molecular subtype (90%), grade (88%), and concurrent use of trastuzumab (87%). The least consensus was for age at which HF-WBI should be offered with 53% of respondents, specifically 73% of academic ROs versus 47% of community ROs (P = .001), agreeing with the guideline. The re-submitted survey 19 months later showed 77% of 287 new respondents now agreed with the guideline regarding age. CONCLUSION: The majority of ROs concur with the 2018 WBI guideline in theMednet surveys, with better agreement among academic ROs than community ROs for certain components of the guideline. Further research into the different practice patterns may optimize patient care.

Management of Isolated Local Failures Following Stereotactic Body Radiation Therapy for Low to Intermediate Risk Prostate Cancer.

Background: Stereotactic body radiation therapy (SBRT) is a safe and effective treatment option for patients with low to intermediate risk prostate cancer (1). SBRT results in very low PSA nadirs secondary to the delivery of high biologically effective doses. Studies reporting on the diagnosis, confirmation, and management of salvageable isolated local failures (ILF) are limited. This study aims to determine the incidence and management approach of ILF after SBRT in a large single institution cohort. Method: All patients with low or intermediate risk localized prostate cancer treated with SBRT at Georgetown University Hospital were eligible for this study. Treatment was delivered using robotic SBRT with doses of 35-36.25 Gy in five fractions. ILF were diagnosed using multiparametric MRI and/or biopsy prompted by rising PSA levels after achieving long-term nadir. Patient's characteristics were extracted from a prospective institutional quality of life trial (IRB 2009-510). Type of salvage therapy and post-salvage PSA were determined on subsequent follow-up and chart review. Results: Between December 2008 to August 2018, 998 men with low to intermediate risk prostate cancer were eligible for inclusion in this analysis. Twenty-four patients (low risk, n = 5; intermediate risk, n = 19) were found to have ILF within the prostate on either MRI (n = 19) and/or biopsy (n = 20). Median pre-treatment PSA was 7.55 ng/ml. Median time to diagnosis of ILF was 72 months (24-110 months) with median PSA at the time of ILF of 2.8 ng/ml (0.7-33 ng/ml). Median PSA doubling time was 17 months (5-47 months). Thirteen patients with biopsy proven ILF proceeded with salvage therapy (cryotherapy n = 12, HIFU n = 1). Of 12 patients who underwent cryotherapy, 7 had a post-treatment PSA of <0.1 ng/ml. One patient experienced a urethral-cutaneous fistula (grade 3 toxicity). Conclusion: The incidence of isolated local recurrence is rare in our cohort. Diagnosis and management of isolated local failures post-SBRT continues to evolve. Our report highlights the importance of early utilization of MRI and confirmatory biopsy at relatively low PSA levels and long PSA doubling time (1). Additionally, undetectable PSA levels after salvage therapy supports the role of early treatment in ILF (1). Further research is needed to determine appropriate patient selection and salvage modality in this population.

A low percentage of metastases in deep brain and temporal lobe structures.

BACKGROUND: Whole-brain radiotherapy (WBRT) in patients with brain metastases (BM) is associated with neurocognitive decline. Given its crucial role in learning and memory, efforts to mitigate this toxicity have mostly focused on sparing radiation to the hippocampus. We hypothesized that BM are not evenly distributed across the brain and that several additional areas may be avoided in WBRT based on a low risk of developing BM. METHODS: We contoured 2757 lesions in a large, single-institution database of patients with newly diagnosed BM. BM centroids were mapped onto a standard brain atlas of 55 anatomic subunits and the observed percentage of BM was compared with what would be expected based on that region's volume. A region of interest (ROI) analysis was performed in a validation cohort of patients from 2 independent institutions using equivalence and one-sample hypothesis tests. RESULTS: The brainstem and bilateral thalami, hippocampi, parahippocampal gyri, amygdala, and temporal poles had a cumulative risk of harboring a BM centroid of 4.83% in the initial cohort. This ROI was tested in 157 patients from the validation cohort and was found to have a 4.1% risk of developing BM, which was statistically equivalent between the 2 groups (P < 1 × 10-6, upper bound). CONCLUSION: Several critical brain structures are at a low risk of developing BM. A risk-adapted approach to WBRT is worthy of further investigation and may mitigate the toxicities of conventional radiation.

Pharmacological Inhibition of the DNA Damage Checkpoint Prevents Radiation-Induced Oocyte Death.

Ovarian function is directly correlated with survival of the primordial follicle reserve. Women diagnosed with cancer have a primary imperative of treating the cancer, but since the resting oocytes are hypersensitive to the DNA-damaging modalities of certain chemo- and radiotherapeutic regimens, such patients face the collateral outcome of premature loss of fertility and ovarian endocrine function. Current options for fertility preservation primarily include the collection and cryopreservation of oocytes or in vitro-fertilized oocytes, but this necessitates a delay in cancer treatment and additional assisted reproductive technology procedures. Here, we evaluated the potential of pharmacological preservation of ovarian function by inhibiting a key element of the oocyte DNA damage checkpoint response, checkpoint kinase 2 (CHK2; CHEK2). Whereas nonlethal doses of ionizing radiation (IR) eradicate immature oocytes in wild-type mice, irradiated Chk2-/- mice retain their oocytes and, thus, fertility. Using an ovarian culture system, we show that transient administration of the CHK2 inhibitor 2-(4-(4-chlorophenoxy)phenyl)-1H-benzimidazole-5-carboxamide-hydrate ("CHK2iII") blocked activation of the CHK2 targets TRP53 and TRP63 in response to sterilizing doses of IR, and preserved oocyte viability. After transfer into sterilized host females, these ovaries proved functional and readily yielded normal offspring. These results provide experimental evidence that chemical inhibition of CHK2 is a potentially effective treatment for preserving the fertility and ovarian endocrine function of women exposed to DNA-damaging cancer therapies such as IR.